Glucose‐6‐phosphate dehydrogenase deficiency and intracranial atherosclerotic stenosis in stroke patients

Abstract

Background and purpose Intracranial atherosclerotic stenosis (ICAS) is a major cause of stroke in Asian countries. Glucose‐6‐phosphate dehydrogenase (G6PD) deficiency, a hereditary enzyme defect prevalent in Asian countries, has been associated with atherosclerotic cardiovascular disease and worse poststroke outcomes. However, the impact of G6PD deficiency on ICAS remains unclear. We aimed to compare the risk of ICAS in stroke patients with and without G6PD deficiency in a Chinese cohort. Methods We prospectively and consecutively recruited stroke patients from four centers in China. All patients received intracranial artery assessment by magnetic resonance/computed tomography angiography or digital subtraction angiography, as well as G6PD enzyme evaluation. The prevalence, burden, and characteristics of ICAS were compared between patients with and without G6PD deficiency using multivariate regression analysis. Results Among 1593 patients, 116 (63.7%) of 182 patients with G6PD deficiency and 714 (50.6%) of 1411 patients with normal G6PD levels were identified as ICAS. Age, hypertension, diabetes, and G6PD deficiency were independent predictors of ICAS. Among patients with ICAS, G6PD‐deficient individuals were more likely to have multiple (≥2 segments) intracranial stenosis (odds ratio [OR] = 1.87, 95% confidence interval [CI] = 1.25–2.81, p = 0.002). G6PD deficiency increased the risk of ICAS in patients who were male (OR = 1.82, 95% CI = 1.24–2.66, p = 0.002), aged ≥70 years (OR = 2.40, 95% CI = 1.33–4.31, p = 0.004), or hypertensive (OR = 1.88, 95% CI = 1.28–2.77, p = 0.001). Conclusions Stroke patients with G6PD deficiency have a higher prevalence and ICAS burden than those with normal G6PD, particularly those who are male, older, and hypertensive.

Metabolomics profiling to characterize cerebral ischemia-reperfusion injury in mice

“…Consistent with our results, it has been demonstrated that ischemia-reperfusion can induce the elevation of the pentose phosphate pathway and associated G6PD activation, which may exhibit a neuroprotective effect via the phosphorylation of heat shock protein 27 ( Yamamoto et al, 2018 ). Furthermore, a recent study suggested that G6PD deficiency leads to poor prognosis and relatively high death rate in patients with cerebral ischemia ( Ou et al, 2020 ; Li et al, 2022 ). Moreover, accumulation of G6P caused by metabolic stress could be redirected from glycolysis into the pentose phosphate pathway to generate NADPH, thus leading to the activation of mTOR, which is greatly involved in neurogenesis ( Lipton and Sahin, 2014 ; Takei and Nawa, 2014 ; LiCausi and Hartman, 2018 ; Karlstaedt et al, 2020 ).…”